Despite all the advances in the health care system, malaria remains a devastating problem in subSaharan Africa. Moreover, resistance to the existing pharmacological agents is the major factor overrating the issue. Therefore, researches to discover newer antimalarial agents having better safety and efficacy are being held. Natural products particularly medicinal plants that are known sources of new drugs and/or lead compounds provide potential options. The root of Euphorbia abyssinica (Euphorbiaceae) is used to treat malaria in some parts of Ethiopia traditionally and the anti-malarial activity of the 80% hydroalcoholic crude extract of the roots has shown a very good antimalarial activity. However, no bioassay-guided fractionation study is conducted yet. Thus, the current study investigated, the anti-plasmodial activities of solvent fractions of the roots of E. abyssinica in mice infected with Plasmodium berghei using the four-day suppressive test. The antimalarial activities of ethyl acetate, methanol, and aqueous fractions of the crude extract of the roots of the plant were evaluated using parameters like; % parasitemia, mean survival time, body weight, rectal temperature and packed cell volume at doses of 100, 200 and 400 mg/kg/day administered orally. Windows SPSS version 25 was used for data analysis. One-way Analysis of variance (ANOVA) followed by Tukey's post hoc test was used to compare data between groups. All the three fractions tested exerted dose-dependent chemosupressive activity. The ethyl acetate fraction showed superior parasite suppression (78.87%) at the highest dose (400 mg/kg/day). The 100 and 200 mg/kg/day doses were also able to produce parasite suppression of 52.43% and 69.57%, respectively. Besides, all the three dose levels of ethyl acetate fraction produced a statistically significant mean survival time (MST) prolongation (p